Based on precise evaluation of hematological findings and clinical manifestations, the relationship between genotype and clinical phenotype was studied in 475 Greek patients with /? and d/~ thalassemias. Almost all known genotypes are included in this series, but the most frequent was homozygous pth high A2 (71.6%), flth/flth silent (7.4%), flth/~/~oth high F (6.30/0) and flth/flth Dutch (6.3%).
In general, the phenotype was related to the genotype, though clinical heterogeneity was detected among patients with the same genotype. The severe type of thalassemia major was most commonly found in homozygous/?th patients mainly of/?~176 and flo//?+ genotypes while homozygous/?+patients had milder clinical manifestation. Furthermore a small group &patients, characterized as homozygous/?++ (HbF < 30%) had mild thalassemia intermedia. In addition mild thalassemia intermedia was principally related with homozygous dflom, and compound heterozygous flth/flth silent I, and less frequently with other genotypes such as compound heterozygous with /~th/flth Dutch,/?th//?th silent II, flth/~floth high F or Lepore.
It was shown that precise genetic characterization and clinical evaluation is of primary importance in predicting the prognosis and formulating the proper treatment for the individual patient with thalassemia.